MicroRNA-138-5p Regulates Hippocampal Neuroinflammation and Cognitive Impairment by NLRP3/Caspase-1 Signaling Pathway in Rats

Feng, Xiaojin; Hu, Jiaying; Zhan, Fenfang; Luo, Deqiang; Hua, Fuzhou; Xu, Guohai

doi:10.2147/jir.s304461

Cited by 31 publications

(22 citation statements)

References 53 publications

(79 reference statements)

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“…Evidence has previously been presented suggesting that increased formation of miR-138-5p is beneficial for the cognitive function of LPS-treated rats, and the reason might be attributed to its suppression of neuroinflammation and neuron cell apoptosis [23]. Besides, Feng et al [24] also propose the close relationship between the downregulation of miR-138-5p and impaired learning and memory in LPS-treated rats, the underlying mechanism might be correlated with its beneficial effect against neuroinflammation. From another perspective, both neuroinflammation and neuronal apoptosis have been indicated to deteriorate neurological function [25].…”

Section: Discussion/conclusionmentioning

confidence: 99%

Dysregulation of Serum miR-138-5p and Its Clinical Significance in Patients with Acute Cerebral Infarction

Mao¹,

Luan²,

Qi³

2022

Cerebrovasc Dis

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Introduction: Acute cerebral infarction (ACI) occurs with the involvement of differential expression of microRNAs. The study detected the expression pattern of miR-138-5p in the serum of ACI cases and evaluated its clinical significance, in an attempt to provide some guidance for the treatment and daily nursing of patients with ACI clinically. Methods: Levels of miR-138-5p in the serum of ACI patients and healthy controls (HCs) were detected via qRT-PCR. Ninety days after treatment, the modified Rankin Scale (mRS) was used to evaluate the prognosis of ACI patients. Receiver operating characteristic (ROC) curve was drawn, and the area under the curve was calculated. The logistic regression analysis was performed to estimate the relationship between various indicators and the clinical outcome. Results: miR-138-5p showed a diminished trend in ACI cases compared with the control group. A significantly negative correlation was detected for serum miR-138-5p with the National Institutes of Health Stroke Scale score in all ACI cases (r = −0.704, p < 0.001). The ROC curve demonstrated the diagnostic potential of serum miR-138-5p to distinguish ACI from HCs. Lessened expression of miR-138-5p was detected in ACI patients with poor prognosis, which can predict the poor prognosis of ACI patients after treatment. Logistic regression analysis determined the independent influence relationship between miR-138-5p and poor prognosis. Conclusion: Diminished miR-138-5p is identified to be a risk factor for the occurrence of ACI, and it is associated with the worse outcome of the patients.

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Section: Discussion/conclusionmentioning

confidence: 99%

Dysregulation of Serum miR-138-5p and Its Clinical Significance in Patients with Acute Cerebral Infarction

Mao¹,

Luan²,

Qi³

2022

Cerebrovasc Dis

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“…miR-138-5p has been found to be a metastatic and tumour suppressor in different types of diseases [ 25 – 29 ]. Our previous study found that miR-138-5p plays a vital role in neuroinflammation by targeting NLRP3 and this phenomenon can cause cognitive impairment [ 30 ]. The NLRP3 protein is a crucial element of the multifunctional inflammasome complex in the inflammatory signalling pathway.…”

Section: Discussionmentioning

confidence: 99%

“…miR-138-5p has been found to be a tumour suppressor in bladder [ 25 ], non-small cell lung [ 26 ], colorectal [ 27 ], malignant glioblastoma [ 28 ], and pancreatic cancer [ 29 ]. Our previous study found that miR-138-5p plays a vital role in cognitive impairment by targeting NLRP3 [ 30 ]. We also predicted that with RNA sequencing (RNA-seq) and bioinformatics analysis, the lncRNA NONRATT004344/miR-138-5p/NLRP3 ceRNA network (ceRNET) could regulate NLRP3-triggered inflammatory responses in ALI [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Suppression of lncRNA NLRP3 inhibits NLRP3-triggered inflammatory responses in early acute lung injury

Luo

Dai²,

Feng

et al. 2021

Cell Death Dis

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Acute lung injury (ALI) is a common lung pathology that is accompanied by alveolar macrophage (AM) activation and inflammatory response. This study investigated the role of the long non-coding RNA NONRATT004344 (hereafter named lncRNA NLRP3) in regulating the Nod-like receptor protein 3 (NLRP3)-triggered inflammatory response in early ALI and the underlying mechanism as well. We established LPS-induced ALI models to explore their interactive mechanisms in vitro and in vivo. Luciferase reporter assays were performed to determine that miR-138-5p could bind to lncRNA NLRP3 and NLRP3. We observed increased lncRNA NLRP3 expression, decreased miR-138-5p expression, NLRP3 inflammasome activation, and upregulated caspase-1, IL-1β, and IL-18 expression in the LPS-induced ALI model. Furthermore, lncRNA NLRP3 overexpression activated the NLRP3 inflammasome and promoted IL-1β and IL-18 secretion; the miR-138-5p mimic abolished these effects in vivo and in vitro. Consistently, miR-138-5p inhibition reversed the effects of lncRNA NLRP3 silencing on the expression of NLRP3-related molecules and inhibition of the NLRP3/caspase-1/IL-1β signalling pathway. Mechanistically, lncRNA NLRP3 sponging miR-138-5p facilitated NLRP3 activation through a competitive endogenous RNA (ceRNA) mechanism. In summary, our results suggested that lncRNA NLRP3 binding miR-138-5p promotes NLRP3-triggered inflammatory response via lncRNA NLRP3/miR-138-5p/NLRP3 ceRNA network (ceRNET) and provides insights into the treatment of early ALI.

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“…MiR-138–5p can directly target the 3′-UTR of NLRP3 and inhibit the expression of NLRP3. Up-regulation of miR-138–5p inhibits the activation of NLRP3/caspase-1 axis and microglia, thereby attenuating hippocampal neuroinflammation and improving the cognitive function of the rat model ( Feng et al, 2021a ). MicroRNA-223 also directly targets and inhibits the expression of NLRP3, thereby reducing LPS-induced inflammation in microglia and improving neuronal function ( Zhang et al, 2020 ).…”

Section: Nlrp3 Inflammasome Inhibitors As a Potential Target For The ...mentioning

confidence: 99%

The Role of NLRP3 Inflammasome in Alzheimer’s Disease and Potential Therapeutic Targets

Liang

Zhang

et al. 2022

Front. Pharmacol.

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Alzheimer’s disease (AD) is a common age-related neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral impairment. The typical pathological characteristics of AD are extracellular senile plaques composed of amyloid ß (Aβ) protein, intracellular neurofibrillary tangles formed by the hyperphosphorylation of the microtubule-associated protein tau, and neuron loss. In the past hundred years, although human beings have invested a lot of manpower, material and financial resources, there is no widely recognized drug for the effective prevention and clinical cure of AD in the world so far. Therefore, evaluating and exploring new drug targets for AD treatment is an important topic. At present, researchers have not stopped exploring the pathogenesis of AD, and the views on the pathogenic factors of AD are constantly changing. Multiple evidence have confirmed that chronic neuroinflammation plays a crucial role in the pathogenesis of AD. In the field of neuroinflammation, the nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is a key molecular link in the AD neuroinflammatory pathway. Under the stimulation of Aβ oligomers and tau aggregates, it can lead to the assembly and activation of NLRP3 inflammasome in microglia and astrocytes in the brain, thereby causing caspase-1 activation and the secretion of IL-1β and IL-18, which ultimately triggers the pathophysiological changes and cognitive decline of AD. In this review, we summarize current literatures on the activation of NLRP3 inflammasome and activation-related regulation mechanisms, and discuss its possible roles in the pathogenesis of AD. Moreover, focusing on the NLRP3 inflammasome and combining with the upstream and downstream signaling pathway-related molecules of NLRP3 inflammasome as targets, we review the pharmacologically related targets and various methods to alleviate neuroinflammation by regulating the activation of NLRP3 inflammasome, which provides new ideas for the treatment of AD.

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MicroRNA-138-5p Regulates Hippocampal Neuroinflammation and Cognitive Impairment by NLRP3/Caspase-1 Signaling Pathway in Rats

Cited by 31 publications

References 53 publications

Dysregulation of Serum miR-138-5p and Its Clinical Significance in Patients with Acute Cerebral Infarction

Dysregulation of Serum miR-138-5p and Its Clinical Significance in Patients with Acute Cerebral Infarction

Suppression of lncRNA NLRP3 inhibits NLRP3-triggered inflammatory responses in early acute lung injury

The Role of NLRP3 Inflammasome in Alzheimer’s Disease and Potential Therapeutic Targets

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